558P - Survival benefit of adjuvant chemotherapy based on molecular residual disease detection in resected colorectal liver metastases: Subgroup analysis from CIRCULATE-Japan GALAXY

Background

The survival benefit of adjuvant chemotherapy (Cx) after surgical resection of colorectal liver metastases (CLM) remains unclear. The prognostic role of circulating-tumor DNA (ctDNA)-based molecular residual disease (MRD) detection was reported recently and a risk-stratification strategy based on monitoring MRD has been proposed in colorectal cancer.

Methods

CLM patients without extrahepatic disease from GALAXY observational study (UMIN000039205) were included. ctDNA was detected using a personalized, tumor-informed 16-plex PCR-NGS assay (Signatera™, Natera, Inc.). MRD status was defined with testing 2 to 10 weeks after curative surgery. The disease-free survival (DFS) benefit of adjuvant Cx was evaluated in MRD-positive and -negative groups, adjusting for age, sex, performance status, T and N status, tissue biomarkers (RAS, BRAF, and MSI), previous history of oxaliplatin for primary cancer, and postoperative complication.

Results

Among 332 CLM patients without extrahepatic disease who underwent curative surgery, 207 did not receive preoperative chemotherapy and were included in this analysis with a median follow of 22.8 months. ctDNA positivity in the MRD window was 33.3% (69/207). Adjuvant Cx was administered to 27.0% (56/207) of patients. In MRD-positive group (N=69), 24-month DFS was higher for patients treated with Cx (Cx (+) vs. Cx (-); 33.3 vs. 4.2%; HR 0.23, [95% CI, 0.12-0.46], p<0.0001); no Cx benefit was seen in the MRD negative group (N=138), (71.6 vs. 58.5%; HR 0.52, [95% CI, 0.25-1.07], p=0.078). Multivariate analysis for DFS showed that T stage (HR 0.41 [0.18-0.94], p=0.036), RAS status wild, (HR 0.52 [0.29-0.93], p=0.028), and Cx (HR 0.24 [0.11-0.50], p<0.0001) were identified as prognostic factors in the MRD-positive group. However, in the MRD-negative group, the benefit of Cx in DFS was limited (HR 0.49 [0.22-1.08], p=0.077).

Conclusions

Our data suggest that the adjuvant chemotherapy benefit in the setting of CLM applies only to MRD-positive patients. Risk stratification strategy based on MRD status can be incorporated in future clinical trials for CLM. OS data will be awaited.

Clinical trial identification

UMIN000039205.

Editorial acknowledgement

Legal entity responsible for the study

CIRCULATE-Japan.

Funding

Natera Inc.

Disclosure

K. Kataoka: Financial Interests, Personal, Invited Speaker: Merck BioPharma, Takeda, Eli Liiy Japan. Y. Nakamura: Financial Interests, Personal, Invited Speaker: Chugai, Merck Biopharma, Guardant Health Pte Ltd, MSD K.K, Eisai, Zeria Pharmaceutical, Miyarisan pharmaceutical, CareNet, Inc., Hisamitsu Pharmaceutical, Taiho Pharmaceutical, DAIICHI SANKYO Co., Ltd., Becton Dickinson, Guardant Health Japan Corp.; Financial Interests, Personal, Advisory Board: Natera, Inc., Roche Ltd., Seagen, Inc., Premo Partners, Inc., DAIICHI SANKYO Co., Ltd., Takeda, Exact Sciences, Gilead Sciences, Guardant Health Pte Ltd; Financial Interests, Institutional, Funding: Taiho, Chugai, Guardant Health, Genomedia, Daiichi Sankyo, Roche Diagnostics, Guardant Health AMEA, Inc., Tempus; Financial Interests, Institutional, Coordinating PI: Seagen. M. Kotaka: Financial Interests, Personal, Invited Speaker: Chugai, Takeda. K. Yamazaki: Financial Interests, Personal, Invited Speaker: Chugai Pharma, Daiichi Sankyo, Yakult Honsha, Takeda, Bayer, Merck Serono, Taiho Pharmaceutical, Lilly, Sanofi, Ono Pharmaceutical, MSD, Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical. Y. Kagawa: Financial Interests, Personal, Invited Speaker: Bayer, Chugai, Ono, Lilly, Merck, Takeda, MSD; Financial Interests, Personal and Institutional, Coordinating PI: Ono. D. Kotani: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Chugai, Daiichi-Sankyo, Eli lilly, MSD, MerckBiopharma, Ono pharma, Pfizer, Taiho pharma, Takeda, Sysmex, Nihonkayaku, Novartis, Guardant Health; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Institutional, Local PI: Ono pharma, MSD, Servier, Novartis, Janssen pharma, IQVIA, Syneos health, CIMIC shiftzero, CIMIC; Financial Interests, Institutional, Funding: Ono pharma. H. Bando: Financial Interests, Institutional, Research Grant: Ono pharmaceutical; Other, Lecture fee: Ono pharmaceutical, Taiho pharmaceutical, Eli Lilly Japan. H. Taniguchi: Financial Interests, Personal, Invited Speaker: Ono, Takeda, Eli Lilly, Chugai, Taiho, Merck Biopharma, Amgen, MSD K.K, Bristol-Myers Squibb Japan, Roche Diagnostics; Financial Interests, Institutional, Coordinating PI: Takeda, Daiichi Sankyo; Financial Interests, Institutional, Local PI: Ono. T. Kato: Financial Interests, Personal, Invited Speaker: CHUGAI PHARMACEUTICAL CO., LTD, Eli Lilly and Company, ONO Pharmaceutical Co, Takeda Pharmaceutical Company Limited; Financial Interests, Institutional, Research Grant: CHUGAI PHARMACEUTICAL CO; Financial Interests, Personal, Coordinating PI: ASAHIKASEI. T. Yoshino: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Bayer Yakuhin, Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal, Other, Consultancy: Sumitomo Corp.; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical Co., Ltd, Sanofi K.K., MSD K.K., Taiho Pharmaceutical Co., Ltd., Molecular Health GmbH, Amgen K.K., Pfizer Japan Inc., Genomedia Inc., Sysmex Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Eisai Co., Ltd., Roche Diagnostics K.K., FALCO Biosystems Ltd., Merus N.V., Bristol-Myers Squibb K.K., Medical & Biological Laboratories Co., LTD., Takeda Pharmaceutical Co., Ltd. E. Oki: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Eli Lilly, Bristol-myers squibb, MSD, Takeda Pham; Financial Interests, Institutional, Research Grant: Guardant Health. All other authors have declared no conflicts of interest.